The purpose of this study is to determine the overall safety of adoptive immunotherapy when
given after chemotherapy for AML/MDS. Adoptive immunotherapy means using an infusion of
cells from a donor to help fight cancer. The donor cells will be either from the umbilical
cord blood of a newborn baby or they will be cells collected from a relative
The 2 cohorts that were discussed - adoptive immunotherapy with either UCB or
haplo-identical stem cells - will be analyzed separately.
Preliminary data from other centers has suggested that adoptive immunotherapy with cells
from a relative is an effective approach that may improve remission rates and survival in
AML and MDS, because they exert anti-cancer effects of their own (so called graft vs
leukemia effects) and possibly because they hasten recovery of cell counts from
chemotherapy. The Investigators are interested in confirming these data, but also in testing
umbilical cord blood cells for the same purpose. Preliminary data indicate that umbilical
cord blood cells may have more powerful graft vs leukemia effects and cause fewer
This is a phase 2 trial to evaluate the safety of adoptive immunotherapy with Non-Inherited
Maternal Antigen (NIMA) compatible, Inherited Paternal Antigen (IPA) targeted CBU or with
haplo-identical stem cells after conventional induction therapy for very high risk Acute
Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS).
The study has 2 cohorts - patients in cohort 1 will receive CBU cells as adoptive
immunotherapy. Patients in cohort 2 will receive haplo-identical cells. Both cohorts will be
evaluated separately and no formal statistical comparison between cohorts will be performed.
There will be approximately 20 patients in each cohort, and a 95% confidence interval for
the proportion of patients experiencing grade III-IV GVHD complications or unexplained
prolonged myelosuppression complications in each cohort can be constructed to be within +/-
13.1% of the observed complication proportions. This calculation assumes an expected
prevalence of each of these complication proportions of no greater than 10%.
After 10 patients are enrolled in each group, the incidence of the above-defined
life-threatening complications will be assessed. If more than one patient out of 10 enrolled
patients (i.e., greater than 10%) in a cohort experiences either of these complications, the
cohort will be stopped for safety.
All potential recipients will have complete HLA typing and determination of HLA antibodies.
An appropriate umbilical cord blood unit (CBU) will be identified or in the absence of an
appropriate CBU, a haplo-identical donor will be identified.
Treatment will be as per the treating physician's choice..
The umbilical cord graft or haplo-graft will be administered between 24 - 72 hours after the
completion of the chemotherapy regimen.
The Graft Selection Algorithm is as follows:
1. CBU Unit 5/6 Matched - 1 NIMA match with patient
2. CBU Unit 5/6 Matched - Shared IPA target(s) with patient
3. Haplo-identical relative
4. CBU Unit 4/6 Matched - 1-2 NIMA matches with patient
5. CBU Unit 4/6 Matched - Shared IPA target(s) with patient
Within 42 days of transplant, the recipient's pre-treatment evaluation includes: medical
history and physical examinations, ECOG, CBC, HLA antibodies, and CMV antibody testing.
Patients will continue with the therapy specified in this protocol until one of the
- Achievement of protocol endpoint CR or CRp after induction and cellular therapy;
- Failure to achieve CR or CRp; or,
- Extraordinary Medical Circumstances: If, at any time the constraints of this protocol
are detrimental to the patient's health and/or the patient no longer wishes to continue
protocol therapy, remove the patient from protocol treatment. In this event.
After removal from protocol therapy, patients will continue to be followed for survival and
disease status. Samples for correlative studies will continue to be collected every two
months until one year after cell infusion.
1. Patients must be 18 years of age or older
2. Patients with a confirmed diagnosis of AML or MDS, according to WHO classification
(excluding acute promyelocytic leukaemia) who have received two or three previous
induction/re-induction regimens. One of the (re-)induction regimens could be stem
cell transplantation (SCT) for achievement of remission. Maintenance and
consolidation (including SCT) may have been given, but are not counted as previous
3. Patients must:
- have never attained CR or CRi (primary refractory); or,
- have failed initial induction therapy, and have attained CR or CRi after salvage
therapy(ies), and then relapsed within < 6 months; or,
- have attained CR or CRi after initial induction therapy and relapsed within <12
months, and failed to respond to salvage therapy(ies); or,
- have relapsed after the latest CR or CRi within < 6 months
4. Patients younger than 60 years should have received previous treatment with
5. Patients must have ECOG performance status (PS) of 0 - 2
6. Women of child-bearing potential must have a negative serum or urine pregnancy test
within 2 weeks prior to treatment start
7. Patients must be capable of understanding and complying with protocol requirements,
and must be able and willing to sign a written informed consent form
1. Persistent clinically significant toxicities from previous chemotherapy
2. Known positive status for human immunodeficiency virus (HIV)
3. Pregnant and nursing patients
4. Uncontrolled intercurrent illness including, but not limited to, uncontrolled
infection, or psychiatric illness/social situations that would limit compliance with
5. Impairment of hepatic or renal function to such an extent that the patient, in the
opinion of the investigator, will be exposed to an excessive risk if entered into
this clinical study
6. Active heart disease including myocardial infarction within previous 3 months,
symptomatic coronary artery disease, arrhythmias not controlled by medication, or
uncontrolled congestive heart failure. Any NYHA grade 3 or 4.
7. Any medical condition which in the opinion of the investigator places the patient at
an unacceptably high risk for toxicities